A recurrent valpha17/vbeta10 TCR-expressing T cell clone is involved in the pathogenicity of collagen-induced arthritis in DBA/1 mice

Eur J Immunol. 1999 Nov;29(11):3636-42. doi: 10.1002/(SICI)1521-4141(199911)29:11<3636::AID-IMMU3636>3.0.CO;2-3.

Abstract

Collagen-induced arthritis (CIA) is an experimental model that mimics clinical and histological features of rheumatoid arthritis. In this disease, a crucial role in initiating the pathological changes has been assigned to T lymphocytes expressing the Th1 phenotype. Aiming at identifying type II collagen (CII)-specific T cells involved in CIA, T cell clones were generated in vitro from the lymph nodes (LN) of CII-immunized DBA / 1 mice. In three independent experiments, we repeatedly isolated CD4(+) Th1 clones recognizing the immunodominant epitope in the CB11 fragment of bovine CII and expressing a unique alpha betaTCR produced by the rearrangement of Valpha17/Jalpha20 and Vbeta10/Dbeta1.1/Jbeta2.5 gene segments. By reverse transcriptase-PCR, we demonstrated the presence of mRNA transcripts specific for the beta complementary-determining region 3 of this clonotype in the LN of the majority (73%) of mice with CIA whereas it was never detected in control animals. When transferred to CII-immunized DBA/1 mice, this recurrent Th1 clone augmented the incidence, aggravated significantly the clinical signs of CIA and greatly enhanced the anti-CII antibody response. Altogether, these results provide evidence that a CD4(+) Th1 clone belonging to the public arm of the response toward the immunodominant epitope of CII is involved in the cascade of events leading to CIA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Arthritis, Rheumatoid / chemically induced
  • Arthritis, Rheumatoid / immunology*
  • Arthritis, Rheumatoid / physiopathology
  • Cattle
  • Clone Cells
  • Collagen
  • Disease Models, Animal
  • Male
  • Mice
  • Mice, Inbred DBA
  • Receptors, Antigen, T-Cell, alpha-beta / immunology*
  • T-Lymphocytes / immunology*

Substances

  • Receptors, Antigen, T-Cell, alpha-beta
  • Collagen

Associated data

  • GENBANK/AF118105